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Catechol-O-Methyltransferase Val158Met Polymorphism Influences Anxiety, Depression, and Disability, but not Pressure Pain Sensitivity, in Women With Fibromyalgia Syndrome

Published:October 01, 2012DOI:https://doi.org/10.1016/j.jpain.2012.08.001

      Abstract

      Our aim was to assess the relationship of the Val158Met polymorphism to pain, anxiety, depression, functional ability, and pressure pain sensitivity in women with fibromyalgia (FMS). One hundred (n = 100) women with FMS diagnosed according to the American College of Rheumatology criteria participated. A numerical pain rate scale (0–10) was used to assess the intensity of pain; the Hospital Anxiety and Depression Scale was calculated to determine anxiety and depression; and functional ability was determined with the Fibromyalgia Impact Questionnaire. Further, pressure pain thresholds (PPTs) were bilaterally assessed over C5-C6 zygapophyseal joints, second metacarpal, and tibialis anterior muscles. Finally, after amplifying Val158Met polymorphisms by polymerase chain reaction, catechol-O-methyltransferase (COMT) genotype was divided into Val/Val, Val/Met, or Met/Met genotypes. Women with FMS with the Met/Met genotype exhibited higher disability (F = 11.836; P < .001), anxiety (F = 13.385; P < .001), and depression (F = 6.931; P = .002) than those with Val/Val and Val/Met genotypes. No differences for the intensity of widespread pain (F = .154; P = .857) and PPT levels over C5-C6 joints (F = 1.014; P = .336), second metacarpal (F = .216; P = .806), and tibialis anterior muscle (F = 1.179; P = .311) were found. Our results suggest that the Val158Met COMT polymorphism modulated some psychological variables but not pressure pain sensitivity in FMS, because women carrying the Met/Met genotype show higher disability, depression, and anxiety but similar PPTs than those with Val/Met or Val/Val genotypes. This study is important because it strives to understand potential genetic factors that predispose some women with FMS to exhibit a more severe phenotypic expression of the disease. Future studies are needed to elucidate potential relevance of the differences.

      Perspective

      This study suggests that the Val158Met COMT polymorphism modulated some psychological variables but not pressure pain sensitivity in FMS because women with FMS carrying the Met/Met genotype exhibit higher disability, depression, and anxiety than but similar PPTs to those with Val/Met and Val/Val genotypes. This study provides further evidence of potential genetic factors that predispose women with FMS to exhibit the disease more severely.

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      References

        • Barbosa F.R.
        • Matsuda J.B.
        • Mazucato M.
        • de Castro França S.
        • Zingaretti S.M.
        • da Silva L.M.
        • Martinez-Rossi N.M.
        • Júnior M.F.
        • Marins M.
        • Fachin A.L.
        Influence of catechol-O-methyltransferase (COMT) gene polymorphisms in pain sensibility of Brazilian fibromialgia patients.
        Rheumatol Int. 2012; 32: 427-430
        • Bennett R.
        The Fibromyalgia Impact Questionnaire (FIQ): A review of its development, current version, operating characteristics and uses.
        Clin Exp Rheumatol. 2005; 23: S154-S156
        • Bijur P.
        • Silveer W.
        • Gallagher J.E.
        Reliability of the visual analogue scale for measurement of acute pain.
        Acad Emerg Med. 2001; 8: 1153-1157
        • Burckhardt C.S.
        • Clark S.R.
        • Bennett R.M.
        The Fibromyalgia Impact Questionnaire: Development and validation.
        J Rheumatol. 1991; 18: 728-733
        • Calandre E.P.
        • García-Carrillo J.
        • García-Leiva J.M.
        • Rico-Villademoros F.
        • Molina-Barea R.
        • Rodríguez López C.M.
        Subgrouping patients with fibromyalgia according to the results of the Fibromyalgia Impact Questionnaire: A replication study.
        Rheumatol Int. 2011; 31: 1555-1559
        • Chesterson L.S.
        • Sim J.
        • Wright C.C.
        • Foster N.E.
        Inter-rater reliability of algometry in measuring pressure pain thresholds in healthy humans, using multiple raters.
        Clin J Pain. 2007; 23: 760-766
        • Cohen H.
        • Neumann L.
        • Glazer Y.
        • Ebstein R.P.
        • Buskila D.
        The relationship between a common Catechol-O-methyltransferase (COMT) polymorphism val (158) met and fibromyalgia.
        Clin Exp Rheumatol. 2009; 27: S51-S56
        • Desmeules J.A.
        • Cedrashi C.
        • Rapiti E.
        • Baymgartner E.
        • Finckh A.
        • Cohen P.
        • Dayer P.
        • Vischer T.L.
        Neurophysiologic evidence for a central sensitization in patients with fibromyalgia.
        Arthritis Rheum. 2003; 48: 1420-1429
        • Desmeules J.
        • Piguet V.
        • Besson M.
        • Chabert J.
        • Rapiti E.
        • Rebsamen M.
        • Rossier M.F.
        • Curtin F.
        • Dayer P.
        • Cedraschi C.
        Psychological distress in fibromyalgia patients: A role for catechol-O-methyl-transferase Val158met polymorphism.
        Health Psychol. 2012; 31: 242-249
        • de Souza J.B.
        • Goffaux P.
        • Julien N.
        • Potvin S.
        • Charest J.
        • Marchand S.
        Fibromyalgia subgroups: proWling distinct subgroups using the Fibromyalgia Impact Questionnaire. A preliminary study.
        Rheumatol Int. 2009; 29: 509-515
        • Diatchenko L.
        • Slade G.D.
        • Nackley A.G.
        • Bhalang K.
        • Sigurdsson A.
        • Belfer I.
        • Goldman D.
        • Xu K.
        • Shabalina S.A.
        • Shagin D.
        • Max M.B.
        • Makarov S.S.
        • Maixner W.
        Genetic basis for individual variations in pain perception and the development of a chronic pain condition.
        Hum Mol Genet. 2005; 14: 135-143
        • Drabant E.M.
        • Hariri A.R.
        • Meyer-Lindenberg A.
        • Munoz K.E.
        • Mattay V.S.
        • Kolachana B.S.
        • Egan M.F.
        • Weinberger D.R.
        Catechol-o-methyltransferase val158met genotype and neural mechanisms related to affective arousal and regulation.
        Arch General Psychiatr. 2006; 63: 1396-1406
        • Egan M.F.
        • Goldberg T.E.
        • Kolachana B.S.
        • Callicott J.H.
        • Mazzanti C.M.
        • Straub R.E.
        • Goldman D.
        • Weinberger D.R.
        Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia.
        Proc Natl Acad Sci USA. 2001; 98: 6917-6922
        • Esteve-Vives J.
        • Rivera-Redondo J.
        • Salvat-Salvat I.
        • Gracia-Blanco M.
        • Alegre-Miguel C.
        Propuesta de una versión de consenso del Fibromyalgia Impact Questionnaire (FIQ) para la población española.
        Reumatol Clin. 2007; 3: 21-24
        • Fernández-de-Las-Peñas C.
        • Fernández-Lao C.
        • Cantarero-Villanueva I.
        • Ambite-Quesada S.
        • Rivas-Martínez I.
        • Del Moral-Avila R.
        • Arroyo-Morales M.
        Catechol-O-methyltransferase genotype (Val158met) modulates cancer-related fatigue and pain sensitivity in breast cancer survivors.
        Breast Cancer Res Treat. 2012; 133: 405-412
        • Finan P.H.
        • Zautra A.J.
        • Davis M.C.
        • Lemery-Chalfant K.
        • Covault J.
        • Tennen H.
        COMT moderates the relation of daily maladaptive coping and pain in fibromyalgia.
        Pain. 2011; 152: 300-307
        • García-Fructuoso F.J.
        • Lao-Villadóniga J.I.
        • Beyer K.
        • Santos C.
        Relationship between catechol-O-methyltransferase genotypes and fibromyalgia severity.
        Reumatol Clin. 2006; 2: 168-172
        • Gürsoy S.
        • Erdal E.
        • Herken H.
        • Madenci E.
        • Alasehirli B.
        • Erdal N.
        Significance of the catechol-O-methyltransferase gene polymorphism in fibromyalgia syndrome.
        Rheumatol Int. 2003; 23: 104-107
        • Hamburg M.A.
        • Collins F.S.
        The path to personalized medicine.
        N Engl J Med. 2010; 363: 301-304
        • Herrero M.J.
        • Blanch J.
        • Pei J.M.
        • De Pablo J.
        • Pintor L.
        • Bulbena A.
        A validation study of the hospital anxiety and depression scale (HADS) in a Spanish population.
        Gen Hosp Psych. 2003; 25: 277-283
        • Herrmann C.
        International experiences with the Hospital Anxiety and Depression Scale–a review of validation data and clinical results.
        J Psychosom Res. 1997; 42: 17-41
        • Holm S.
        A simple sequentially rejective multiple test procedure.
        Scand J Stat. 1979; 6: 65-70
        • Jacobsen L.M.
        • Eriksen G.S.
        • Pedersen L.M.
        • Gjerstad J.
        Catechol-O-methyltransferase (COMT) inhibition reduces spinal nociceptive activity.
        Neurosci Lett. 2010; 473: 212-215
        • Jensen M.P.
        • Turbner J.A.
        • Romano J.M.
        • Fisher L.
        Comparative reliability and validity of chronic pain intensity measures.
        Pain. 1999; 83: 157-162
        • Khasar S.G.
        • Green P.G.
        • Miao F.J.
        • Levine J.D.
        Vagal modulation of nociception is mediated by adrenomedullary epinephrine in the rat.
        Eur J Neurosci. 2003; 17: 909-915
        • Lee Y.H.
        • Choi S.J.
        • Ji J.D.
        • Song G.G.
        Candidate gene studies of fibromyalgia: A systematic review and meta-analysis.
        Rheumatol Int. 2012; 32: 417-426
        • Mannisto P.
        • Kaakkola S.
        Catechol-O-methyltransferase (COMT): Biochemistry, molecular biology, pharmacology, and clinical efficacy of the new selective COMT inhibitors.
        Pharmacol Rev. 1999; 51: 593-628
        • Matsuda J.B.
        • Barbosa F.R.
        • Morel L.J.
        • França Sde C.
        • Zingaretti S.M.
        • da Silva L.M.
        • Pereira A.M.
        • Marins M.
        • Fachin A.L.
        Serotonin receptor (5-HT 2A) and catechol-O-methyltransferase (COMT) gene polymorphisms: Triggers of fibromyalgia?.
        Rev Bras Reumatol. 2010; 50: 141-149
        • McLean S.A.
        • Diatchenko L.
        • Lee Y.M.
        • Swor R.A.
        • Domeier R.M.
        • Jones J.S.
        • Jones C.W.
        • Reed C.
        • Harris R.E.
        • Maixner W.
        • Clauw D.J.
        • Liberzon I.
        Catechol-o-methyltransferase haplotype predicts immediate musculoskeletal neck pain and psychological symptoms after motor vehicle collision.
        J Pain. 2011; 12: 101-107
        • Montoya P.
        • Pauli P.
        • Batra A.
        • Wiedemann G.
        Altered processing of pain-related information in patients with fibromyalgia.
        Eur J Pain. 2005; 9: 293-303
        • Nackley A.G.
        • Tan K.T.
        • Fecho K.
        • Flood P.
        • Diatchenko L.
        • Maixner W.
        Catechol-O-methyltransferase inhibition increases pain sensitivity through activation of both b2- and b3-adrenergic receptors.
        Pain. 2007; 128: 199-208
        • Nagel I.E.
        • Chicherio C.
        • Li S.C.
        • von Oertzen T.
        • Sander T.
        • Villringer A.
        • Heekeren H.P.
        • Bäckman L.
        • Lindenberger U.
        Human aging magnifies genetic effects on executive functioning and working memory.
        Front Hum Neurosci. 2008; 2: 1
        • Petzke F.
        • Clauw D.J.
        • Ambrose K.
        • Khine A.
        • Gracely R.H.
        Increased pain sensitivity in fibromyalgia: Effects of stimulus type and mode of presentation.
        Pain. 2003; 105: 403-413
        • Rakvag T.T.
        • Ross J.R.
        • Sato H.
        • Skorpen F.
        • Kaasa S.
        • Klepstad P.
        Genetic variation in the Catechol-O-methyltransferase (COMT) gene and morphine requirements in cancer patients with pain.
        Mol Pain. 2008; 4: 64
        • Small B.J.
        • Rawson K.S.
        • Walsh E.
        • Jim H.S.
        • Hughes T.F.
        • Iser L.
        • Andrykowski M.A.
        • Jacobsen P.B.
        Catechol-O-methyltransferase genotype modulates cancer treatment-related cognitive deficits in breast cancer survivors.
        Cancer. 2011; 117: 1369-1376
        • Smolka M.N.
        • Schumann G.
        • Wrase J.
        • Grüsser S.M.
        • Flor H.
        • Mann K.
        • Braus D.F.
        • Goldman D.
        • Büchel C.
        • Heinz A.
        Catechol-o-methyltransferase val158met genotype affects processing of emotional stimuli in the amygdala and prefrontal cortex.
        J Neuros. 2005; 25: 836-842
        • Staud R.
        • Rodriguez M.
        Mechanisms of disease: Pain in fibromyalgia syndrome.
        Nat Clin Pract Rheumatol. 2006; 2: 90-98
        • Staud R.
        Predictors of clinical pain intensity in patients with fibromyalgia syndrome.
        Curr Pain Headache Rep. 2005; 9: 316-321
        • Strous R.D.
        • Bark N.
        • Woerner M.
        • Lachman H.M.
        Lack of association of a functional catechol-O-methyltransferase gene polymorphism in schizophrenia.
        Biol Psychiatry. 1997; 41: 493-495
        • Syvanen A.C.
        • Tilgmann C.
        • Rinne J.
        • Ulmanen I.
        Genetic polymorphism of catechol-O-methyltransferase (COMT): Correlation of genotype with individual variation of SCOMT activity and comparison of the allele frequencies in the normal population and parkinsonian patients in Finland.
        Pharmacogenetics. 1997; 7: 65-71
        • Tander B.
        • Gunes S.
        • Boke O.
        • Alayli G.
        • Kara N.
        • Bagci H.
        • Canturk F.
        Polymorphisms of the serotonin-2A receptor and catechol-O-methyltransferase genes: A study on fibromyalgia susceptibility.
        Rheumatol Int. 2008; 28: 685-691
        • Vanderweeen L.
        • Oostendorp R.B.
        • Vaes P.
        • Duquet W.
        Pressure algometry in manual therapy.
        Man Ther. 1996; 1: 258-265
        • Vargas-Alarcón G.
        • Fragoso J.M.
        • Cruz-Robles D.
        • Vargas A.
        • Vargas A.
        • Lao-Villadóniga J.I.
        • García-Fructuoso F.
        • Ramos-Kuri M.
        • Hernández F.
        • Springall R.
        • Bojalil R.
        • Vallejo M.
        • Martínez-Lavín M.
        Catechol-O-methyltransferase gene haplotypes in Mexican and Spanish patients with fibromyalgia.
        Arthritis Res Ther. 2007; 9: R110
        • Wolfe F.
        • Smythe H.A.
        • Yunus M.B.
        • Bennett R.M.
        • Bombardier C.
        • Goldenberg D.L.
        • Tugwell P.
        • Campbell S.M.
        • Abeles M.
        • Clark P.
        The American College of Rheumatology 1990 criteria for classification of fibromyalgia: Report of the multicenter criteria committee.
        Arthritis Rheum. 1990; 33: 160-170
        • Wolfe F.
        • Clauw D.J.
        • Fitzcharles M.A.
        • Goldenberg D.L.
        • Katz R.S.
        • Mease P.
        • Russell A.S.
        • Russell I.J.
        • Winfield J.B.
        • Yunus M.B.
        The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity.
        Arthr Care Res. 2010; 62: 600-610
        • Zigmond A.S.
        • Snaith R.P.
        The hospital anxiety and depression scale.
        Acta Psychiatr Scand. 1983; 67: 361-370
        • Zubieta J.K.
        • Heitzeg M.M.
        • Smith Y.R.
        • Bueller J.A.
        • Xu K.
        • Xu Y.
        • Koeppe R.A.
        • Stohler C.S.
        • Goldman D.
        COMT val158 met Genotype affects μ-opioid neurotransmitter responses to a pain stressor.
        Science. 2003; 299: 1240-1243